Stroke induces ischemic injury in the brain and is a leading cause of neurological disability and death in this country. Prevention and early treatment of ischemic injury are of great significance in reducing the devastating effects on individuals and their families. However, the related strategies are still limited so far. Recently, traditional Chinese medicine has advocated the use of acupuncture or electro-acupuncture (EA) to treat acute stroke. Since this modality is relatively convenient, low-costing and low-risk, it may be a useful therapeutic option. However, its efficacy has not been subjected to scientific testing and the underlying mechanisms are unknown. Therefore, this laboratory has begun to determine the efficacy of EA-induced protection against the effect of brain ischemia and explore the molecular mechanisms with multiple approaches. The initial studies demonstrated that EA significantly attenuated the size of ischemic infarction in the cortex and striatum. Functional studies also showed that EA greatly promoted the recovery of somatosensory evoked potential and electroencephalograms. These observations suggest that EA may be an effective strategy for protection from the effect of cerebral ischemia. Additional work from this laboratory has suggested that delta-opioid receptor (DOR) protects neurons against excitotoxic/hypoxic injury and its expression may be associated with stress tolerance. Since previous work from this laboratory and those of others have shown that EA up- regulates brain opioid activity, and the cortex and striatum have the highest DOR density in the brain, it is possible that DOR serves as an inherent protector in the brain and EA up-regulates DOR activity to protect the brain against the effect of cerebral ischemia. Based on the preliminary data, this proposal will specifically test two major hypotheses: 1) EA protects against cerebral ischemia depending on acupuncture conditions (acupoints, stimulation intensity and time window of EA application, etc.) And 2) EA protection is mediated by the DOR system in the brain. The outcome data may have important clinical implications and provide a guideline for EA application. More importantly, this work will open up a new research field. The understanding of the molecular mechanisms underlying EA-induced protection will eventually lead to develop new solutions for ischemic brain injury.